This invention pertains to new alkylbenzoylbenzofurans and more particularly to new 2-alkyl-3-(4-hydroxy-3,5-di-tert-butylbenzoyl)benzofurans useful for treating cardiac arrhythmia, as well as pharmaceutical compositions containing these benzofurans and the method of treating cardiac arrhythmia therewith.
Cardiac arrhythmia is an important cause of death following myocardial infarction or from other cardiac pathology. Heretofore, drugs used to control this disorder such as quinidine, lidocaine and procainamide have manifested significant drawbacks. According to Goodman and Gilman, The Pharmacologic Basis of Therapeutics, 7th edition, pp.761-770, "About one third of the patients who receive quinidine will have immediate adverse effects that necessitate discontinuation of therapy . . . . Procainamide is useful for the treatment of a variety of arrhythmias, and it can be administered by several routes. Unfortunately its potency and versatility are marred by its short duration of action and high incidence of adverse reactions when it is used chronically . . . . Lidocaine has a narrow antiarrhythmic spectrum . . . . The main adverse effects are on the central nervous system . . . . Higher concentrations may cause decreased hearing disorientation, muscle twitich, convulsions or respiratory arrest."
The great need for improved antiarrhythmics is evident.
According to Gubin et al., Eur. J. Med. Chem.-Chim. Ther.(1974) 9, 19-25, 2-alkyl-3-(4-hydroxy-3,5-dialkylbenzoyl)benzofurans, wherein the 3,5-dialkyl groups each contain 1-3 carbon atoms, are useful intermediates for the preparation of antianginal agents, comprised of the corresponding 2-alkyl(aminoalkyloxy-3,5-dialkylbenzoyl)benzofurans. As is well known in the art, angina results from a narrowing of the coronary blood vessels, usually due to accumulation of plaque, whereas arrhythmia, i.e. irregular heart beat, is a result of a problem with the natural pacemaker. No cardiac activity of any kind has been attributed to 2-alkyl-3-(4-hydroxy-3,5-dialkylbenzoyl)benzofurans by Gubin et al.